The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.

三阴性乳腺癌 (TNBC) 的发展受到某些称为间充质干细胞/基质细胞 (MSC) 的肿瘤微环境相关细胞的严格调控，我们和其他人已经证明，这些细胞通过激活邻近癌症中的促恶性信号传导来促进 TNBC 进展细胞。这些级联的表征将更好地理解 TNBC 生物学，并带来消除与晚期疾病相关的发病率和死亡率的治疗方法。在这里，我们专注于称为长链非编码 RNA 或 lncRNA 的新兴 RNA 类别，并利用 MSC 支持的 TNBC 进展模型来识别与 TNBC 发病机制功能相关的特定家族成员。事实上，虽然有些人被描述为在 TNBC 中发挥功能性作用，lncRNA 作为肿瘤微环境驱动的 TNBC 发展的介质的活性仍有待充分探索。我们报告说，MSC 刺激 LINC01119 在 TNBC 细胞中的强烈表达，这反过来又诱导细胞因子信号转导 5 (SOCS5) 的抑制因子，从而加速癌细胞生长和肿瘤发生。我们表明 LINC01119 和 SOCS5 在多个乳腺癌基因组之间表现出紧密相关性，并且它们在 TNBC 患者队列中高度丰富。重要的是，我们提供的证据表明 LINC01119-SOCS5 轴代表了 TNBC 患者不良结局的强大预后指标，并证明其抑制会严重损害癌细胞生长。共，